title: The effect of bioartificial constructs that mimic myocardial structure and biomechanical properties on stem cell commitment towards cardiac lineage.
abstract: Despite the enormous progress in the treatment of coronary artery diseases, they remain the most common cause of heart failure in the Western countries. New translational therapeutic approaches explore cardiomyogenic differentiation of various types of stem cells in combination with tissue-engineered scaffolds. In this study we fabricated PHBHV/gelatin constructs mimicking myocardial structural properties. Chemical structure and molecular interaction between material components induced specific properties to the substrate in terms of hydrophilicity degree, porosity and mechanical characteristics. Viability and proliferation assays demonstrated that these constructs allow adhesion and growth of mesenchymal stem cells (MSCs) and cardiac resident non myocytic cells (NMCs). Immunofluorescence analysis demonstrated that stem cells cultured on these constructs adopt a distribution mimicking the three-dimensional cell alignment of myocardium. qPCR and immunofluorescence analyses showed the ability of this construct to direct initial MSC and NMC lineage specification towards cardiomyogenesis: both MSCs and NMCs showed the expression of the cardiac transcription factor GATA-4, fundamental for early cardiac commitment. Moreover NMCs also acquired the expression of the cardiac transcription factors Nkx2.5 and TBX5 and produced sarcomeric proteins. This work may represent a new approach to induce both resident and non-resident stem cells to cardiac commitment in a 3-D structure, without using additional stimuli.
authors.affiliation: Institute for Composite and Biomedical Materials, C.N.R., o.u. Pisa, Pisa, Italy. Electronic address: caterina.cristallini@diccism.unipi.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cristallini
authors.forename: Elisa
authors.initials: E
authors.lastname: Cibrario Rocchietti
authors.forename: Lisa
authors.initials: L
authors.lastname: Accomasso
authors.forename: Anna
authors.initials: A
authors.lastname: Folino
authors.forename: Clara
authors.initials: C
authors.lastname: Gallina
authors.forename: Luisa
authors.initials: L
authors.lastname: Muratori
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rastaldo
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.forename: Silvia
authors.initials: S
authors.lastname: Saviozzi
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Sprio
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Gagliardi
authors.forename: Niccoletta
authors.initials: N
authors.lastname: Barbani
authors.forename: Claudia
authors.initials: C
authors.lastname: Giachino
mesh_terms: D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds
keywords: 3-D; Biocompatibility; Cardiac tissue engineering; Cell morphology; ECM; ECM (extracellular matrix); MSCs; NMCs; PHBHV; Scaffold; Stem cell; extracellular matrix; mesenchymal stem cells; non myocytic cells; poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid); three-dimensional